IDHC_MICOH
ID IDHC_MICOH Reviewed; 414 AA.
AC Q9Z2K8;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Isocitrate dehydrogenase [NADP] cytoplasmic;
DE Short=IDH;
DE Short=IDH1;
DE EC=1.1.1.42 {ECO:0000250|UniProtKB:O88844};
DE AltName: Full=Cytosolic NADP-isocitrate dehydrogenase;
DE AltName: Full=IDPc;
DE AltName: Full=NADP(+)-specific ICDH;
DE AltName: Full=Oxalosuccinate decarboxylase;
GN Name=IDH1; Synonyms=IDP2;
OS Microtus ochrogaster (Prairie vole).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Arvicolinae; Microtus.
OX NCBI_TaxID=79684;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=9866202; DOI=10.1093/oxfordjournals.molbev.a025894;
RA Nekrutenko A., Hillis D.M., Patton J.C., Bradley R.D., Baker R.J.;
RT "Cytosolic isocitrate dehydrogenase in humans, mice, and voles and
RT phylogenetic analysis of the enzyme family.";
RL Mol. Biol. Evol. 15:1674-1684(1998).
CC -!- FUNCTION: Catalyzes the NADP(+)-dependent oxidative decarboxylation of
CC isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate),
CC which is required by other enzymes such as the phytanoyl-CoA
CC dioxygenase (By similarity). Plays a critical role in the generation of
CC NADPH, an important cofactor in many biosynthesis pathways (By
CC similarity). May act as a corneal epithelial crystallin and may be
CC involved in maintaining corneal epithelial transparency (By
CC similarity). {ECO:0000250|UniProtKB:O75874,
CC ECO:0000250|UniProtKB:Q9XSG3}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH;
CC Xref=Rhea:RHEA:19629, ChEBI:CHEBI:15562, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.42;
CC Evidence={ECO:0000250|UniProtKB:O88844};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19630;
CC Evidence={ECO:0000250|UniProtKB:O88844};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O88844};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:O88844};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit.
CC {ECO:0000250|UniProtKB:O88844};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:O88844}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P41562}.
CC -!- PTM: Acetylation at Lys-374 dramatically reduces catalytic activity.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
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DR EMBL; AF048832; AAD02925.1; -; Genomic_DNA.
DR RefSeq; XP_005361517.1; XM_005361460.2.
DR AlphaFoldDB; Q9Z2K8; -.
DR SMR; Q9Z2K8; -.
DR Ensembl; ENSMOCT00000024306; ENSMOCP00000020484; ENSMOCG00000018153.
DR GeneID; 101996438; -.
DR CTD; 3417; -.
DR OrthoDB; 769322at2759; -.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005777; C:peroxisome; IEA:Ensembl.
DR GO; GO:0004450; F:isocitrate dehydrogenase (NADP+) activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0006103; P:2-oxoglutarate metabolic process; ISS:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; IEA:Ensembl.
DR GO; GO:0006097; P:glyoxylate cycle; IEA:UniProtKB-KW.
DR GO; GO:0006102; P:isocitrate metabolic process; ISS:UniProtKB.
DR GO; GO:0071071; P:regulation of phospholipid biosynthetic process; IEA:Ensembl.
DR GO; GO:0060696; P:regulation of phospholipid catabolic process; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR004790; Isocitrate_DH_NADP.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR PANTHER; PTHR11822; PTHR11822; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR PIRSF; PIRSF000108; IDH_NADP; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR00127; nadp_idh_euk; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 3: Inferred from homology;
KW Acetylation; Cytoplasm; Glyoxylate bypass; Magnesium; Manganese;
KW Metal-binding; NADP; Oxidoreductase; Phosphoprotein;
KW Tricarboxylic acid cycle.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT CHAIN 2..414
FT /note="Isocitrate dehydrogenase [NADP] cytoplasmic"
FT /id="PRO_0000083577"
FT BINDING 75..77
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 77
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 82
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 94..100
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 109
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 132
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 212
FT /ligand="substrate"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT BINDING 252
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 260
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 275
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 279
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 310..315
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT BINDING 328
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT SITE 139
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250"
FT SITE 212
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT MOD_RES 42
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT MOD_RES 81
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 126
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 224
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 233
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 243
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 321
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O75874"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
FT MOD_RES 400
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88844"
SQ SEQUENCE 414 AA; 46694 MW; D8ECB6F9D9B87331 CRC64;
MSKKIHGGSV VEMQGDEMTR IIWELIKEKL ILPYVELDLH SYDLGIENRD ATNDQVTKDA
AEAIKKYNVG VKCATITPDE KRVEEFKLKQ MWKSPNGTIR NILGGTVFRE AIICKNIPRL
VTGWVKPIII GRHAYGDQYR ATDFVVPGPG KVEITYTPKD GSQKVTYLVH SFEEGGGVAM
GMYNQDKSIE DFAHSSFQMA LSKGWPLYLS TKNTILKKYD GRFKDIFQEI YDKQYKSQFE
AQKIWYEHRL IDDMVAQAMK SEGGFIWACK NYDGDVQSDS VAQGYGSLGM MTSVLICPDG
KTVEAEAAHG TVTRHYRMHQ KGQETSTNPI ASIFAWSRGL AHRARLDNNT ELSFFAKALE
EVCIETIEAG FMTKDLAACI KGLPNVQRSD YLNTFEFMDK LGENLKAKLA QAKL
